Campylobacter gene polymorphism as a determinant of clinical features of Guillain-Barre syndrome
Campylobacter gene polymorphism as a determinant of clinical features of Guillain-Barre syndrome
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DOI：
10.1212/01.wnl.0000176914.70893.14
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发表时间：
2005-11-08
期刊：
影响因子：
9.9
通讯作者：
Yuki, N
中科院分区：
文献类型：
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作者：
Koga, M;Takahashi, M;Yuki, N
背景：空肠弯曲菌的神经节苷脂表位被认为是格林-巴利综合征(GBS)发生和特征的关键，但尚未建立一个全面的理论。C空肠基因Cst-II参与神经节苷脂低聚糖的生物合成，具有影响神经节苷脂表位的多态(Asn/Thr51)。目的：验证该基因多态性决定自身抗体反应性的假说，从而确定GBS的神经学表现。方法：收集105例GBS(包括其变异型)和65例无并发症肠炎患者的空肠分离株。作者检测了CST-II的频率和多态(ASN/Thr51)与细菌神经节苷脂表位、抗GM1、GD1a和GQ1b的自身抗体反应性以及患者的神经学结果有关。结果：神经源性菌株Cst-II，尤其是Cst-II(Thr51)的发生率高于肠源性菌株(85%vs52%；p<；0.001)。携带CST-II(Asn51)的菌株通常表达GQ1b表位(83%)，而携带CST-II(Thr51)的菌株通常表达GM1(92%)和GD1a(91%)表位。神经病患者中这些细菌表位的存在与自身抗体的反应性相对应。空肠弯曲菌(Asn51)感染者抗GQ1bIg G抗体阳性率较高(56%vs8%；p<；0.001)，有眼瘫(%vs13%；p<；0.001)和共济失调(42%vs11%；p=0.001)。空肠多发(Thr51)的患者抗GM1抗体(88%vs35%；p<；0.001)和抗GD1aIg G抗体(52%vs24%；p=0.006)和肢体无力(98%vs71%；p<；0.001)。结论：空肠C基因多态性决定了自身抗体的反应性和格林-巴利综合征(GBS)的临床表现，可能是通过宿主模拟分子的修饰来实现的。GBS范式是第一个解释感染后、自身免疫介导的分子模仿触发疾病的详细发病机制的范例。
Background: Ganglioside epitopes on Campylobacter jejuni are hypothesized as the key to the development and characterization of Guillain-Barre syndrome (GBS), but a comprehensive theory has yet to be established. A C jejuni gene, cst-II, involved in the biosynthesis of ganglioside-like lipo-oligosaccharide, shows a polymorphism (Asn/Thr51) that affects ganglioside epitopes. Objective: To examine the hypothesis that this polymorphism determines autoantibody reactivity, and thereby neurologic presentations in GBS. Methods: C jejuni isolates were collected from 105 GBS (including its variants) and 65 uncomplicated enteritis patients. The authors examined the frequency of cst-II and polymorphism (Asn/Thr51) in connection with the bacterial ganglioside epitopes, autoantibody reactivities against GM1, GD1a, and GQ1b, and patients' neurologic findings. Results: Neuropathic strains more frequently had cst-II, in particular cst-II (Thr51), than did enteritic ones (85% vs 52%; p < 0.001). Strains with cst-II (Asn51) regularly expressed the GQ1b epitope (83%), whereas those with cst-II (Thr51) had the GM1 (92%) and GD1a (91%) epitopes. The presence of these bacterial epitopes in neuropathy patients corresponded to autoantibody reactivity. Patients infected with C jejuni (Asn51) more often were positive for anti-GQ1b IgG (56% vs 8%; p < 0.001) and had ophthalmoparesis (64% vs 13%; p < 0.001) and ataxia (42% vs 11%; p = 0.001). Patients who had C jejuni (Thr51) more frequently were positive for anti- GM1 (88% vs 35%; p < 0.001) and anti- GD1a IgG (52% vs 24%; p = 0.006) and had limb weakness (98% vs 71%; p < 0.001). Conclusions: The genetic polymorphism of C jejuni determines autoantibody reactivity as well as the clinical presentation of Guillain - Barre syndrome (GBS), possibly through modification of the host- mimicking molecule. The GBS paradigm is the first to explain the detailed pathogenesis of a postinfectious, autoimmune-mediated, molecular mimicry-triggering disorder.